The objective of this pilot clinical trial is to improve the results and capability of islet transplantation early in the course of type 1 diabetes through the implementation of selective immunomodulatory therapy for the prevention of islet allograft rejection. Unparalleled progress in the conceptual understanding of the mechanism operative in the induction of transplantation tolerance has led to the development of novel immunomodulatory strategies. The demonstration of long term islet allograft survival in totaly pancreatectomized rhesus monkeys treated with the anti-CD40 Ligand (anti-CD154) specific monoclonal antibody 5c8 is a prime example of progress made. These unprecedented results were obtained in the absence of clinically evident side effects and laboratory abnormalities. Furthermore, anti-CD154 antibody therapy displayed no inhibition of signaling through the CD154:CD40 costimulatory pathway utilizing this humanized monoclonal antibody now provides a realistic opportunity for major advances in clinical islet transplantation. We hypothesize that the safety and efficacy of anti-CD154 antibody monotherapy as demonstrated in the relevant preclinical non-human primated model will translate into clinical trials. To test this hypothesis, we request permission to perform the clinical trial entitled "An Open Labe, Multi-Center Study to Determine the Safety of Therapy with Biogen's Anti-CD 40 Ligand Antibody (BG 9588) in Subject Receiving Islet Cell Transplantation". This clinical trial directly correlates to specific Aim 1.2 of the JDFI grant entitled "Novel Immunotherapy Towards Safe and successful Islet Replacement in Early diabetes". The GCRC will be asked to provide the structure necessary to conduct this clinical research protocol. We will use both the in and out patient beds in carrying out this protocol. Patients will be admitted to CRC 2-3 days before the islet cell transplant and remain hospitalized for 10 days after the transplant. Patients will return to CRC for nine outpatient follo up visits after their islet cell transplant. The CRC nursing staff is needed to provide the careful monitoring necessary to maintain blood glucoses in normoglycemic range pre and post transplant. Nursing expertise will also be relied on for precise collection of research specimens and careful monitoring of patients after their islet transplant and following administration of BG9588.